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Validating a New Severity Score System for Adults With Type 1 Gaucher Disease (GD1)

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ClinicalTrials.gov Identifier: NCT01136304
Recruitment Status : Completed
First Posted : June 3, 2010
Last Update Posted : June 1, 2015
Information provided by (Responsible Party):

Study Description
Brief Summary:
With the participation of an international consortium of investigators, the investigators will evaluate the validity of a new severity score system called DS3 for adult patients with Gaucher disease. The investigators hypothesize that initial DS3 scores will be predictive of both disease progression and patterns of response including imiglucerase dose sensitivity and completeness and maintenance of response and that sequential DS3 scores will accurately portray either clinical progression of disease or improvement in response to treatment. The investigators will also collect DNA specimens that in future research will be used in conjunction with the DS3 scores to evaluate determinants of the clinical course and the response to treatments for Gaucher disease.

Condition or disease Intervention/treatment
Gaucher Disease Drug: Imiglucerase

Detailed Description:

GD1 is a prototypical lysosomal storage disorder and the first disorder to have compelling evidence of successful treatment with enzyme replacement therapy. The common clinical manifestations are hematologic cytopenias, hepatomegaly, splenomegaly, and a spectrum of skeletal pathologies. Disease expression is diverse. The rate and extent of disease progression are variable and often independent of the age at which symptoms are first reported1. Despite a long history of treatment efficacy2, there is significant heterogeneity of response among patients with regard to the maximum improvement in hematologic, visceral, bone, and other manifestations and the dynamic speed of response during therapy1-3. There have been few well-designed studies that comprehensively annotate phenotypic variation over time or measure treatment efficacy and dose response. In part, this is attributable to lack of a validated disease severity scoring system for GD1 to standardize the monitoring of progression and treatment response and to define patient cohorts in clinical studies.

DS3 is a method of expressing an integrated assessment of the burden of disease in a given patient. It can be used to monitor patient status, determine endpoints in clinical studies, classify disease phenotypes and compare patients with the same disease. Although frequently referred to as 'disease severity indices,' DS3 instruments may also include measures of disease activity and damage. DS3s utilize a minimal data set to score the patient in a comprehensive manner. They usually are structured as a group of domains (often according to organ system) that are populated with non-redundant items that are valid, reliable, use feasible, standardized methods of assessment, and that are variably weighted based on associated morbidity and mortality. A DS3 for adult GD1 patients was recently developed and subjected to successful preliminary testing for validity, reliability and feasibility4. With respect to changes over time, a minimal clinically important difference was defined. Construct validity has been partially demonstrated. Using 20 patient profiles from the International Collaborative Gaucher Group (ICGG) Gaucher Registry, the instrument was shown to correlate very well with the "gold standard" clinical global impression scale. However, larger scale testing in a population that is representative of the world wide distribution of GD1 phenotypes (including splenectomy patients) is needed and predictive validity has yet to be determined. Moreover, the DS3 has not yet been correlated with disease-specific measures of response such as achievement of therapeutic goals or broadly used biomarkers. Combining retrospective and prospective analysis, this study is designed to address these issues

Study Design

Study Type : Observational
Actual Enrollment : 173 participants
Observational Model: Cohort
Official Title: Retrospective and Prospective Validation of a Disease Severity Score System (DS3) for Adults With Type 1 Gaucher Disease (GD1)
Study Start Date : April 2010
Primary Completion Date : December 2013
Study Completion Date : December 2013

Groups and Cohorts

Group/Cohort Intervention/treatment
Adults with Type 1 Gaucher disease (GD1)
Adults with GD1 who are cared for at one of the participating research sites whether treatment naive or treated in past or currently with imiglucerase enzyme replacement treatment.
Drug: Imiglucerase
Imiglucerase intravenous infusions regardless of dose or schedule of administration.
Other Name: Cerezyme

Outcome Measures

Primary Outcome Measures :
  1. Change in total DS3 severity score from baseline score [ Time Frame: Calculated annually and assessed up to 25 years until either death, withdrawal from the study, or end of study ]
    The DS3 score is calculated annually from either date of first treatment or, in untreated patients, from date of first enrollment in the ICGG Gaucher Registry

Biospecimen Retention:   Samples With DNA
Whole blood Buccal smears

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Consenting adult patients with type 1 Gaucher disease who are cared for at one of the participating research sites and who are enrolled in the International Collaborative Gaucher Group Gaucher Registry

Inclusion Criteria:

  • Adult patients with Type 1 Gaucher disease regardless of treatment status who are enrolled in the International Collaborative Gaucher Group (ICCG) Gaucher Registry and who are cared for at one of the participating research sites.

Exclusion Criteria:

  • Children under the age of 18 years

    • Patients with Type 3 Gaucher disease
    • Patients who have declined to be enrolled in the ICCG Gaucher Registry
    • Patients not cared for at one of the participating research sites
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01136304

United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211
United States, Florida
Northwest Oncology Hematology Associates PA
Coral Springs, Florida, United States, 33065
Sponsors and Collaborators
University Research Foundation for Lysosomal Storage Diseases, Inc.
University of Pittsburgh
Principal Investigator: Neal J Weinreb, MD University Research Foundation for Lysosomal Storage Diseases, Inc.
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Neal J Weinreb. MD, Principal Investigator, University Research Foundation for Lysosomal Storage Diseases, Inc.
ClinicalTrials.gov Identifier: NCT01136304     History of Changes
Other Study ID Numbers: URFLSD-2010-01
First Posted: June 3, 2010    Key Record Dates
Last Update Posted: June 1, 2015
Last Verified: May 2015

Keywords provided by Neal J Weinreb. MD, University Research Foundation for Lysosomal Storage Diseases, Inc.:
Gaucher disease
Severity score

Additional relevant MeSH terms:
Gaucher Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders